Plasma from Preeclamptic Women Causes a Rapid, Calcium-Sensitive Release of Nitric Oxide from Vascular Smooth Muscle Cells

Abstract

Objective: To determine whether the augmented pressor response in preeclampsia could be due to reduced vascular smooth muscle cell release of the vasodilator nitric oxide, consequent to a circulating plasma factor(s).Methods: The study examined effect of 2% plasma from 14 patients with preeclampsia and 14 normal pregnant women on nitric oxide production (measured as the stable nitrite metabolite) by rat pulmonary artery vascular smooth muscle cells.Results: Plasma from patients with preeclampsia resulted in greater nitric oxide production. The factor(s) in plasma from patients with preeclampsia responsible for stimulating production was sensitive to acid, heat, and proteases, and was removed by charcoal stripping. The effect of exposure to plasma was rapid (maximal production within 30 min) and differed from the time course observed after exposure to cytokines. Nitric oxide production was increased by the calcium ionophore A23187, and the differential effect of plasma from patients with preeclampsia was inhibited by a calmodulin inhibitor. Inhibitors of nitric oxide synthase (N-methyl-L-arginine and aminoguani-dine) reduced nitric oxide production. Western analysis identified only the inducible nitric oxide synthase isoform. Inhibition of protein synthesis did not affect nitric oxide production.Conclusions: Exposure of vascular smooth muscle cells to a circulating factor(s) in the plasma of patients with preeclampsia resulted in a rapid calcium/calmodulin-sensitive increase in nitric oxide production. Characterization studies suggested that this was via an effect on the inducible nitric oxide synthase isoform, which was present prior to exposure to plasma.